The physiological role of glucagon-like peptide-1 7-36 amide (GLP-1 7-36) in man was investigated. GLP-1 7-36-like immunoreactivity was found in the human bowel; its circulating level rose after oral glucose and after a test breakfast. When it was infused into seven volunteers at a rate to mimic its postprandial plasma concentration in the fasting state, plasma insulin levels rose significantly and glucose and glucagon concentrations fell. During an intravenous glucose load, it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations, compared with a control saline infusion, even inducing postinfusion reactive hypoglycaemia. By comparison, infusion of glucose-dependent insulinotropic peptide (GIP) to physiological levels was less effective in stimulating insulin release. These observations suggest that GLP-1 7-36 is a physiological incretin and that it is more powerful than GIP. The observation of greatly increased postprandial plasma GLP-1 7-36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder.